11-19202232-G-A

Variant names:

• chr11-19202232-G-A
• rs12222160
• ENST00000533783.2:c.-117-190C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000533783.2(CSRP3):​c.-117-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 152,280 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.033 (115 hom., cov: 33)
• Consequence: CSRP3 ENST00000533783.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

Genes affected

CSRP3 (HGNC:2472): (cysteine and glycine rich protein 3) This gene encodes a member of the CSRP family of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this protein is found in a group of proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Mutations in this gene are thought to cause heritable forms of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in humans. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

CSRP3-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-19202232-G-A is Benign according to our data. Variant chr11-19202232-G-A is described in ClinVar as [Benign]. Clinvar id is 1247269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP3-AS1	NR_183675.1	n.207+5313G>A		intron_variant	Intron 1 of 5
CSRP3	NM_003476.5	c.-307C>T		upstream_gene_variant		ENST00000265968.9	NP_003467.1
CSRP3	NM_001369404.1	c.-307C>T		upstream_gene_variant			NP_001356333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP3	ENST00000265968.9	c.-307C>T		upstream_gene_variant		1	NM_003476.5	ENSP00000265968.3

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4981 AN: 152162 Hom.: 114 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0328 AC: 4991 AN: 152280 Hom.: 115 Cov.: 33 AF XY: 0.0335 AC XY: 2496 AN XY: 74468

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.0900

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0245 Hom.: 10

Bravo AF: 0.0337

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12222160; hg19: chr11-19223779;